The long-term objective of this research project is to investigate the functional role of olivocochlear (OC) efferent feedback. The OC system originates in the superior olivary complex and projects both to the cochlea and the cochlear nucleus. The first specific aim will examine if efferent activity is instrumental in maintaining auditory attention. Experiments will be conducted with control and transgenic mice in which the gene encoding for the cochlear alpha9 nicotinic acetylcholine receptor (nAChR) subunits have been knocked out. Physiological studies have shown that these mutant mice exhibit normal afferent responses but show no obvious cochlear efferent activity because cholinergic OC projections cannot function in the absence of (9 receptor subunits. Subjects will perform a demanding listening task in which their auditory attention will be directed by a band-limited masker to a variable portion of the frequency spectrum. It is hypothesized that control mice will have better detection and discrimination rates for stimuli presented within the frequency region of the noise band masker compared to those presented outside of the band, while knock-out mice should have similar thresholds regardless of the center frequency of the noise band, since the latter mice should not be able to focus auditory attention. The second specific aim will differentiate contributions of central and peripheral efferent fibers to signal processing in noise, by comparing the hearing thresholds of (9 nAChR subunit normal knock-out mice with those of knock-outs whose OC projections to the cochlear nucleus have been surgical severed, in the same listening task described for Specific Aim 1. It is hypothesized that knockout subjects that lack only peripheral efferent innervations will hear better in this noisy, unpredictable environment compared to their cohorts that have central OC lesions in addition to peripheral de-efferentation. The final specific aim will evaluate the hypothesis that the OC efferent system protects the ear from acoustic over stimulation. Subjects used in these experiments will include control and transgenic mice that have an over expression of the cochlear alpha9 nAChR subunits. This novel transgenic preparation, in combination with planned electrophysiological and behavioral experimental methodologies, represents a unique opportunity to characterize the extent of the protection afforded by the OC system. A better understanding of the brain's acoustic feedback system will aid in the design of assertive devices for human listeners whose efferent function has been compromised.